90 research outputs found

    Thriving under Stress: Selective Translation of HIV-1 Structural Protein mRNA during Vpr-Mediated Impairment of eIF4E Translation Activity

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    Translation is a regulated process and is pivotal to proper cell growth and homeostasis. All retroviruses rely on the host translational machinery for viral protein synthesis and thus may be susceptible to its perturbation in response to stress, co-infection, and/or cell cycle arrest. HIV-1 infection arrests the cell cycle in the G2/M phase, potentially disrupting the regulation of host cell translation. In this study, we present evidence that HIV-1 infection downregulates translation in lymphocytes, attributable to the cell cycle arrest induced by the HIV-1 accessory protein Vpr. The molecular basis of the translation suppression is reduced accumulation of the active form of the translation initiation factor 4E (eIF4E). However, synthesis of viral structural proteins is sustained despite the general suppression of protein production. HIV-1 mRNA translation is sustained due to the distinct composition of the HIV-1 ribonucleoprotein complexes. RNA-coimmunoprecipitation assays determined that the HIV-1 unspliced and singly spliced transcripts are predominantly associated with nuclear cap binding protein 80 (CBP80) in contrast to completely-spliced viral and cellular mRNAs that are associated with eIF4E. The active translation of the nuclear cap binding complex (CBC)-bound viral mRNAs is demonstrated by ribosomal RNA profile analyses. Thus, our findings have uncovered that the maintenance of CBC association is a novel mechanism used by HIV-1 to bypass downregulation of eIF4E activity and sustain viral protein synthesis. We speculate that a subset of CBP80-bound cellular mRNAs contribute to recovery from significant cellular stress, including human retrovirus infection

    Consensus statement on abusive head trauma in infants and young children

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    Abusive head trauma (AHT) is the leading cause of fatal head injuries in children younger than 2 years. A multidisciplinary team bases this diagnosis on history, physical examination, imaging and laboratory findings. Because the etiology of the injury is multifactorial (shaking, shaking and impact, impact, etc.) the current best and inclusive term is AHT. There is no controversy concerning the medical validity of the existence of AHT, with multiple components including subdural hematoma, intracranial and spinal changes, complex retinal hemorrhages, and rib and other fractures that are inconsistent with the provided mechanism of trauma. The workup must exclude medical diseases that can mimic AHT. However, the courtroom has become a forum for speculative theories that cannot be reconciled with generally accepted medical literature. There is no reliable medical evidence that the following processes are causative in the constellation of injuries of AHT: cerebral sinovenous thrombosis, hypoxic-ischemic injury, lumbar puncture or dysphagic choking/vomiting. There is no substantiation, at a time remote from birth, that an asymptomatic birth-related subdural hemorrhage can result in rebleeding and sudden collapse. Further, a diagnosis of AHT is a medical conclusion, not a legal determination of the intent of the perpetrator or a diagnosis of murder. We hope that this consensus document reduces confusion by recommending to judges and jurors the tools necessary to distinguish genuine evidence-based opinions of the relevant medical community from legal arguments or etiological speculations that are unwarranted by the clinical findings, medical evidence and evidence-based literature

    Effect of Alteration Zones on Water Quality: A Case Study from Biga Peninsula, Turkey

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    Widespread and intense zones of silicified, propylitic, and argillic alteration can be found in the Çan volcanics of Biga Peninsula, northwest Turkey. Most of the springs in the study area surface out from the boundary between fractured aquifer (silicified zone) and impervious boundary (argillic zone). This study focuses on two such springs in KirazlI area (KirazlI and Balaban springs) with a distinct quality pattern. Accordingly, field parameters (temperature, pH, and electrical conductivity), major anion and cation (sodium, potassium, calcium, magnesium, chloride, bicarbonate, and sulfate), heavy metals (aluminum, arsenic, barium, chromium, cobalt, cupper, iron, lithium, manganese, nickel, lead, and zinc), and isotopes (oxygen-18, deuterium, and tritium) were determined in water samples taken from these springs during 2005 through 2007. The chemical analyses showed that aluminum concentrations were found to be two orders of magnitude greater in KirazlI waters (mean value 13813.25 μg/L). The levels of this element exceeded the maximum allowable limits given in national and international standards for drinking-water quality. In addition, Balaban and KirazlI springs are >55 years old according to their tritium levels; KirazlI spring is older than Balaban spring. KirazlI spring is also more enriched than Balaban spring based in oxygen-18 and deuterium values. Furthermore, KirazlI spring water has been in contact with altered rocks longer than Balaban spring water, according to its relatively high chloride and electrical conductivity values.TÜBİTA
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